| Project/Area Number |
20J20737
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Single-year Grants |
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| Section | 国内 |
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| Review Section |
Basic Section 90120:Biomaterials-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
Abd Elwakil Mahmoud 北海道大学, 生命科学院, 特別研究員(PD)
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| Project Period (FY) |
2020-04-24 – 2023-03-31
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| Project Status |
Declined (Fiscal Year 2022)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2022: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2021: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2020: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | mRNA drugs / ionizable polyesters / Gene Therapy / Organocatalysis / Lipid Nanoparticles / Lung diseases / Combinatorial chemistry / Immunotherapy / Biomaterials |
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| Outline of Research at the Start |
The general outline of my research includes three main principles
1. Directed evolution of nanocarriers for specific non liver gene delivery.
2. Establishment of rapid and robust screening method to enable in vivo reprogramming of specific cells or tissues on-demand.
3. Understand the biology of CNS delivery and discover the associated endogenous proteins.
Upon having a proof of concept for the previously mentioned concepts, we can introduce a new exciting era for nucleic acid therapeutics. Understanding of those three core principles we will lead to evolve a new field namely; Nanoinformatics.
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| Outline of Annual Research Achievements |
During the past year I have developed a novel platform for mRNA delivery beyond the hepatocytes referred as to ionizable polyester/polyether RNA-Transporters (iPORT LNP). The key findings for the past year are:
1. Development of ionizable lipo-polyether RNA transporters (iPORTs) that are produced via the organocatalytic ring-opening polymerization of glycidylamine monomers using steroidal initiators. Interestingly, the tacticity of the iPORTs had a significant impact on in vitro and in vivo RNA delivery efficiency and tropism and this impact was dependent of monomeric structure. The top performing Estriol-GA05-30 iPORT LNPs elicited strong antitumor activity in a therapeutic, prophylactic model and were well-tolerated in mice. This technology is being filed as a patent through Hokkaido University. Additionally a manuscript has been submitted to JACS, Manuscript ID: ja-2022-017103).
2. Development of ionizable polyester RNA-Transporters LNP that selectively transfect splenocytes and lungs after systemic administration. The results of this project is being filed as a patent through Hokkaido University as well. Furthermore, a manuscript is being prepared for submission to publications.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Although we are at very hard times during COVID-19, my research projects were going very well and research output was really great because:
1. I have submitted two patents in one year.
2. Two manuscripts were prepared and are being submitted for publication in top tier scientific journals.
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| Strategy for Future Research Activity |
In the coming year I plan to:
1. Apply my mRNA iPORT LNP technology for therapeutic application in lung diseases, cancer immunotherapy and infectious diseases vaccines such as COVID-19.
2. Extend my combinatorial chemistry for RNA delivery for other hard tissues such as bone and central nervous system.
3. Communicate my iPORT LNP technology with scientific community via attending international conferences and big pharmaceutical companies.
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